A major regulatory point in the biosynthesis of tetrapyrrolic pigments like chlorophyll and heme is the formation of the building block 5-aminolevulinic acid (ALA) which provides all the carbon and nitrogen atoms of the tetrapyrrole ring. There are two different routes by which ALA is synthesized in the living cell. In animals, fungi and some eubacteria, succinyl-CoA and glycine are condensed by ALA synthase to yield ALA with the concomitant liberation of the carboxyl carbon of glycine as carbon dioxide. In contrast, in plants, algae and certain eubacteria, ALA is formed from Glu-tRNAGlu via two enzymatic reactions (Jahn et al. (1992) Trends Biochem Sci 17:215-218). First, Glu-tRNA reductase converts Glu-tRNAGlu to glutamate 1-semialdehyde (GSA) with the concomitant release of tRNAGlu. GSA aminotransferase then converts GSA to ALA.
Given the facts that plants and animals differ in the way they synthesize ALA and that ALA is an essential compound for survival, it is envisioned that inhibitors of Glu-tRNA reductase and GSA aminotransferase may serve as effective herbicides that are nontoxic to man and other animals. Genes encoding Glu-tRNA reductase and GSA aminotransferase may be isolated and then overexpressed in bacterial or yeast hosts to provide the huge amounts of protein that is needed for inhibitor discovery and design.